Watching bacteria evolve into problems

The rise of antibiotic resistance is old news by now—everyone knows that bacteria evolve in response to their surroundings to maintain, and enhance, their pathogenicity. What's less clear is exactly how this happens. Although we can identify genetic mutations in bacteria, it has been difficult to determine which of those mutations are adaptive and which are just random and neutral. Such knowledge would be mighty useful for identifying the biochemical pathways that are important for disease and can be targeted by therapies.

People with cystic fibrosis are highly prone to long-term bacterial infections. In the 1990s, a rare pathogen called Burkholderia dolosa infected 39 people with cystic fibrosis in a hospital in Boston. Tami Lieberman and her colleagues collected bacterial isolates from the airways and blood of 14 of these people over 16 years. These 112 isolates allowed them to analyze the bacteria's evolution in each individual. Results are reported in this week’s issue of Nature Genetics.

To investigate the pathogen’s evolution, the researchers first looked for isolates with known pathogenic behaviors and then correlated those behaviors with genetic changes. So those isolates that were resistant to the antibiotic ciprofloxacin all shared the same mutation, which occurred after the initial infection in six different subjects. Separately, isolates that were highly virulent had altered structures in their outer membranes. There were two different genetic mutations that yielded the same structure; these mutations arose independently in nine subjects.

Although useful, this approach is limited because it relies on first knowing the selective pressure driving evolution. The researchers really wanted to identify genes under selection without first knowing why they were being selected—that is, things that enhance virulence by a mechanism that we haven't characterized yet. But how do you identify a gene when you don't necessarily know what it does?

The researchers took a stab at the problem. They figured that genes would mutate independently in multiple subjects, so they counted the number of mutations in each bacterial gene in each patient. They found seventeen genes that had multiple mutations. Assuming neutral evolution, without any selective pressure, the expectation would be that only one of the 5,014 bacterial genes would have more than one mutation. Therefore, most of these mutations probably provided an adaptive advantage.

To confirm that these genes were not just "mutational hotspots" (areas prone to picking up mutations at random), the authors looked at the impact of the changes. Most turned out to be nonsynonymous—that is, not only do they change the genetic sequence, but that change alters the protein encoded by the gene. In fact, there were 18 times as many nonsynonymous mutations as would be predicted by genetic drift. Two of the genes identified this way were the ones mentioned above that conferred resistance to ciprofloxacin and altered the outer membrane structure, which validates the approach.

Six of the genes had never before been implicated in pathogenicity. Three of them are involved in oxygen-dependent gene regulation, and the other three don't look much like any protein we know about, so their functions and potential roles in pathogenicity remain unclear. But their identification as having undergone selective pressure while infecting people with cystic fibrosis implies that they merit further attention.

"The rise of antibiotic resistance is old news by now—everyone knows that bacteria evolve in response to their surroundings to maintain, and enhance, their pathogenicity."

No and no. Not everyone knows this, and it isn't true. It is not to enhance their pathogenicity, it is to enhance their ability to reproduce. Often this means to DECREASE their pathogenicity. It is better to be a symbiont that allows your host to thrive than to kill your host.

Similarly, so-called "neutral" mutations are mutations that we do not perceive to be selective. But under another situation they might be. Resistance to Cipro would be neutral or even deleterious until that drug was used.

Furthermore, bacteria thrive in a community, with a cloud of genotypes competing and cooperating. I am not certain that one can determine whether these infections can be traced back to a single organism, and are spared any further contribution from their environment over the duration of the "experiment". Life is more complicated than described here.

So the results are interesting, but this analysis is overly simplified.

Evolution in action in your lungs. Bukrholderia is one of my favorite microbes for sure, but not all of them are pathogenic. Many just live happily in the soil but there is something in CF patients that make them good opportunistics pathogens. This was a nice study with sensitive enough tools to detect SNPs.

"No and no. Not everyone knows this, and it isn't true. It is not to enhance their pathogenicity, it is to enhance their ability to reproduce."

Thank you! The author lost me right off the bat in the first paragraph, and I was going to log in to correct the glaring misconception of evolutionary mechanisms.

To say "bacteria evolve to enhance their pathogenicity" is approaching the question from an anthropocentric (man-centered) viewpoint: setting aside our status as the dominant species on the Planet, bacteria do NOT think about us, or drive their own evolution to make us sicker! In fact, in the case of use of antibiotics, we're the ones polluting THEIR environment, and those that have expressed appropriate drug-resistant genes will survive, and the rest don't. WE, us humans, create bacterial drug resistance: humans are the actors in "natural selection" in this case.

Unfortunately, the provided answer is closer, but still no ceegar.. Bacteria don't evolve to "enhance their ability to reproduce": again, that gives them credit for directing their own evolution (which isn't the case). Instead, species produce random variations without any given direction (where genetic drift is the randomizing element), and "natural selection" takes it from there at times.... Individuals within a species which are better able to survive to reproductive age pass on their DNA to their offspring, who in turn presumably are adapted to their environment, as well.

People who think Evolution is nothing but mumbo jumbo should read these papers.

People who do not believe in evolution generally lack the knowledge required to understand academic research papers. So for that matter does the general public. Even if they could, they would still not believe in evolution - it requires you to choose "faith" over empirical evidence.

Getting back on topic, we need a way to counter bacteria antibiotic resistance or we're someday going to find ourselves in a "post-antibiotic" age. Plus, research into alternatives like bacteriophages needs to be explored more.

People who think Evolution is nothing but mumbo jumbo should read these papers.

People who think evolution is nothing but mumbo jumbo used to surprise me by saying "Of course we believe in resistant bacteria! Even we don't deny that!" And then they'd try to spin it somehow as the "information" for resistance having always been there so it's not a novel feature, or they'd uncritically parrot "adaptation is not evolution!" as if that meant something, or they'd accept microevolution but deny that it can generate new species, etc. Basically most of them have developed some kind of bullshit-flavored coating so they can nominally accept evolution on the scale of increased resistance in disease and pests, yet still deny it enough to be comfortable in the belief that "great grandma wasn't a monkey." And not every branch of anti-evolutionism uses the same coating; there are many mutually-incompatible bullshit flavors to choose from. Though that doesn't stop many of them from holding two or three contradictory mis-rebuttals at once. There are many moves in their repertoire of mental gymnastics for trying to work around it, but basically it all comes back to selective ignorance.

“Colour is skin deep”, so the saying goes but for those imbued with Depth within the sense and not just its Width/Sense, the reality is beyond its simplistic declaration. Width is about what you can see, oka Might or Extremity whereas Depth is beyond what you are able to see because it has true weight/gravity, that of the underlying reality which shadows and is a superset of The Material, The Spiritual.

Colour is only skin deep because all are born equally [at conception] with exactly the same Subtle System ...